Details of the Drug

General Information of Drug (ID: DM2YGNW)

Drug Name

Dactinomycin

Synonyms

Cosmegen; Dactinomicina; Dactinomycine; Dactinomycinum; Meractinomycin; ACT D; ACTINOMYCIN D AMP; Actactinomycin A IV; Actinomycin A IV; Actinomycin Aiv; Actinomycin I; Actinomycin IV; Actinomycin cl; Actinomycin x i; Antibiotic from Streptomyces parvullus; Chounghwamycin B; D Actinomycin; Dactinomycin D; Dactinomyein d; Dilactone actin omycindioic D acid; Dilactone actinomycin D acid; Dilactone actinomycindioic D acid; Lyovac cosmegen; Oncostatin K; Actinomycin 11 cosmegen; Actinomycin 7; Actinomycin C1; Actinomycin I1; Actinomycin X 1; Actinomycin X1; HBF 386; HBF 386 meractinomycin; X 97; AD (VAN); Actinomycin C (sub1); Actinomycin C(sub1); Actinomycin D (JP15); Actinomycin D, sodium deoxyribonucleic acid complex; Actinomycin I (sub1); Actinomycin I(sub 1); Actinomycin I(sub1); Actinomycin-IV; Actinomycindioic D acid, dilactone; Acto-D; COSMEGEN (TN); Dactinomicina [INN-Spanish]; Dactinomycin (USP); Dactinomycin [USAN:BAN]; Dactinomycine [INN-French]; Dactinomycinum [INN-Latin]; NP-005932; Actinomycin D deriv. of 3H-phenoxaocardazine; GNF-PF-1977; Actinomycin-[threo-val-pro-sar-meval]; Actinomyein-theo-val-pro-sar-meval; Actinomycin-(threo-val-pro-sar-meval); O)-(1-oxo-1,2-ethanediyl)]bis(N-methyl)L-valine; PXZ-THR-DVA-PRO-SAR-MVA-THR-DVA-PRO-SAR-MVA; DVA-DPR-SAR-MVA-(c1)DTH-PXZ-(c11)DTH-DVA-DPR-SAR-MVA; 1H-Pyrrolo(2,1-1)-(1,4,7,10,13)oxatetraazacyclohexadecine; 4,6-dimethyl-3-oxo-3H-phenoxazine-1,9-dicarboxamide

Indication

Disease Entry	ICD 11	Status	REF
Adult kidney Wilms tumor	N.A.	Approved	[1]
Advanced cancer	2A00-2F9Z	Approved	[1]
Beckwith-Wiedemann syndrome	N.A.	Approved	[1]
Childhood kidney Wilms tumor	N.A.	Approved	[1]
Gestational trophoblastic neoplasia	2F33-2F76	Approved	[1]
Hamartoma	N.A.	Approved	[1]
Solid tumour/cancer	2A00-2F9Z	Approved	[2]
Wilms tumor	N.A.	Approved	[1]
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Therapeutic Class

Anticancer Agents

Drug Type

Small molecular drug

Structure

3D MOL is unavailable

2D MOL

#Ro5 Violations (Lipinski): 2

Molecular Weight (mw)

1255.4

Logarithm of the Partition Coefficient (xlogp)

3.8

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption: The drug is poorly absorbed from gastrointestinal tract []
BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [3]
Elimination: 10% of drug is excreted from urine in the unchanged form [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 36 hours [4]
Metabolism: The drug is metabolized via the hepatic []
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.01195 micromolar/kg/day [5]
Water Solubility: The ability of drug to dissolve in water is measured as 0.5 mg/mL [3]

Adverse Drug Reaction (ADR)

ADR Term	Variation	Related DOT	DOT ID	REF
Cell-mediated cytotoxicity	Not Available	HYAL1	OT2SJN0X	[6]
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Chemical Identifiers

Formula: C62H86N12O16
IUPAC Name: 2-amino-4,6-dimethyl-3-oxo-1-N,9-N-bis[(3R,6S,7R,10S,16S)-7,11,14-trimethyl-2,5,9,12,15-pentaoxo-3,10-di(propan-2-yl)-8-oxa-1,4,11,14-tetrazabicyclo[14.3.0]nonadecan-6-yl]phenoxazine-1,9-dicarboxamide
Canonical SMILES: C[C@@H]1[C@@H](C(=O)N[C@@H](C(=O)N2CCC[C@H]2C(=O)N(CC(=O)N([C@H](C(=O)O1)C(C)C)C)C)C(C)C)NC(=O)C3=C4C(=C(C=C3)C)OC5=C(C(=O)C(=C(C5=N4)C(=O)N[C@H]6[C@H](OC(=O)[C@@H](N(C(=O)CN(C(=O)[C@@H]7CCCN7C(=O)[C@H](NC6=O)C(C)C)C)C)C(C)C)C)N)C
InChI: InChI=1S/C62H86N12O16/c1-27(2)42-59(84)73-23-17-19-36(73)57(82)69(13)25-38(75)71(15)48(29(5)6)61(86)88-33(11)44(55(80)65-42)67-53(78)35-22-21-31(9)51-46(35)64-47-40(41(63)50(77)32(10)52(47)90-51)54(79)68-45-34(12)89-62(87)49(30(7)8)72(16)39(76)26-70(14)58(83)37-20-18-24-74(37)60(85)43(28(3)4)66-56(45)81/h21-22,27-30,33-34,36-37,42-45,48-49H,17-20,23-26,63H2,1-16H3,(H,65,80)(H,66,81)(H,67,78)(H,68,79)/t33-,34-,36+,37+,42-,43-,44+,45+,48+,49+/m1/s1
InChIKey: RJURFGZVJUQBHK-IIXSONLDSA-N

Cross-matching ID

PubChem CID: 457193
ChEBI ID: CHEBI:27666
CAS Number: 50-76-0
DrugBank ID: DB00970
TTD ID: D0P8IV
VARIDT ID: DR01203
ACDINA ID: D00983

Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Breaker	[7]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[8]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[9]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[10]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
14-3-3 protein sigma (SFN)	OTLJCZ1U	1433S_HUMAN	Gene/Protein Processing	[11]
All-trans-retinol 13,14-reductase (RETSAT)	OTC3AOPX	RETST_HUMAN	Gene/Protein Processing	[11]
Antigen peptide transporter 1 (TAP1)	OTJL27PW	TAP1_HUMAN	Gene/Protein Processing	[11]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Gene/Protein Processing	[11]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Gene/Protein Processing	[12]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Drug Response	[13]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Gene/Protein Processing	[12]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Gene/Protein Processing	[14]
BSD domain-containing protein 1 (BSDC1)	OT853CP9	BSDC1_HUMAN	Gene/Protein Processing	[11]
CASP8 and FADD-like apoptosis regulator (CFLAR)	OTX14BAS	CFLAR_HUMAN	Gene/Protein Processing	[15]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Dactinomycin (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Roflumilast	DMPGHY8	Moderate	Additive immunosuppressive effects by the combination of Dactinomycin and Roflumilast.	Asthma [CA23]	[16]
Ofloxacin	DM0VQN3	Minor	Decreased absorption of Dactinomycin due to intestinal mucosa variation caused by Ofloxacin.	Bacterial infection [1A00-1C4Z]	[17]
Sparfloxacin	DMB4HCT	Minor	Decreased absorption of Dactinomycin due to intestinal mucosa variation caused by Sparfloxacin.	Bacterial infection [1A00-1C4Z]	[17]
Gemifloxacin	DMHT34O	Minor	Decreased absorption of Dactinomycin due to intestinal mucosa variation caused by Gemifloxacin.	Bacterial infection [1A00-1C4Z]	[17]
Norfloxacin	DMIZ6W2	Minor	Decreased absorption of Dactinomycin due to intestinal mucosa variation caused by Norfloxacin.	Bacterial infection [1A00-1C4Z]	[17]
ABT-492	DMJFD2I	Minor	Decreased absorption of Dactinomycin due to intestinal mucosa variation caused by ABT-492.	Bacterial infection [1A00-1C4Z]	[17]
Levofloxacin	DMS60RB	Minor	Decreased absorption of Dactinomycin due to intestinal mucosa variation caused by Levofloxacin.	Bacterial infection [1A00-1C4Z]	[17]
Lomefloxacin	DMVRH9C	Minor	Decreased absorption of Dactinomycin due to intestinal mucosa variation caused by Lomefloxacin.	Bacterial infection [1A00-1C4Z]	[17]
Teriflunomide	DMQ2FKJ	Major	Additive immunosuppressive effects by the combination of Dactinomycin and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[18]
Denosumab	DMNI0KO	Moderate	Additive myelosuppressive effects by the combination of Dactinomycin and Denosumab.	Low bone mass disorder [FB83]	[19]
Thalidomide	DM70BU5	Major	Additive thrombogenic effects by the combination of Dactinomycin and Thalidomide.	Multiple myeloma [2A83]	[20]
Tecfidera	DM2OVDT	Moderate	Additive immunosuppressive effects by the combination of Dactinomycin and Tecfidera.	Multiple sclerosis [8A40]	[21]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Dactinomycin and Siponimod.	Multiple sclerosis [8A40]	[22]
Fingolimod	DM5JVAN	Major	Additive immunosuppressive effects by the combination of Dactinomycin and Fingolimod.	Multiple sclerosis [8A40]	[23]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Dactinomycin and Ocrelizumab.	Multiple sclerosis [8A40]	[24]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Dactinomycin and Ozanimod.	Multiple sclerosis [8A40]	[16]
Omacetaxine mepesuccinate	DMPU2WX	Moderate	Additive immunosuppressive effects by the combination of Dactinomycin and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[25]
Gatifloxacin	DMSL679	Minor	Decreased absorption of Dactinomycin due to intestinal mucosa variation caused by Gatifloxacin.	Respiratory infection [CA07-CA4Z]	[17]
Canakinumab	DM8HLO5	Moderate	Additive immunosuppressive effects by the combination of Dactinomycin and Canakinumab.	Rheumatoid arthritis [FA20]	[26]
Rilonacept	DMGLUQS	Moderate	Additive immunosuppressive effects by the combination of Dactinomycin and Rilonacept.	Rheumatoid arthritis [FA20]	[26]
Golimumab	DMHZV7X	Major	Additive immunosuppressive effects by the combination of Dactinomycin and Golimumab.	Rheumatoid arthritis [FA20]	[27]
Leflunomide	DMR8ONJ	Major	Additive immunosuppressive effects by the combination of Dactinomycin and Leflunomide.	Rheumatoid arthritis [FA20]	[18]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of Dactinomycin when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[28]
Fostamatinib	DM6AUHV	Moderate	Decreased clearance of Dactinomycin due to the transporter inhibition by Fostamatinib.	Thrombocytopenia [3B64]	[29]
Azathioprine	DMMZSXQ	Moderate	Additive myelosuppressive effects by the combination of Dactinomycin and Azathioprine.	Transplant rejection [NE84]	[22]
Ganciclovir	DM1MBYQ	Moderate	Additive myelosuppressive effects by the combination of Dactinomycin and Ganciclovir.	Virus infection [1A24-1D9Z]	[22]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Water	E00035	962	Solvent
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Dactinomycin 0.5mg/1ml lyophilized powder	0.5mg/1ml	Lyophilized Powder	Intravenous

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References

1	Dactinomycin FDA Label
2	FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 050682.
3	BDDCS applied to over 900 drugs
4	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
6	ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
7	Structural studies of atom-specific anticancer drugs acting on DNA. Pharmacol Ther. 1999 Sep;83(3):181-215.
8	Expression of multidrug resistance-associated protein in NIH/3T3 cells confers multidrug resistance associated with increased drug efflux and altered intracellular drug distribution. Cancer Res. 1995 Nov 15;55(22):5342-7.
9	Breast cancer resistance protein (BCRP/ABCG2) induces cellular resistance to HIV-1 nucleoside reverse transcriptase inhibitors. Mol Pharmacol. 2003 Jan;63(1):65-72.
10	Potential role of drug transporters in the pathogenesis of medically intractable epilepsy. Epilepsia. 2005 Feb;46(2):224-35.
11	Genomic profiling uncovers a molecular pattern for toxicological characterization of mutagens and promutagens in vitro. Toxicol Sci. 2011 Jul;122(1):185-97.
12	Actinomycin D upregulates proapoptotic protein Puma and downregulates Bcl-2 mRNA in normal peripheral blood lymphocytes. Anticancer Drugs. 2007 Aug;18(7):763-72. doi: 10.1097/CAD.0b013e3280adc905.
13	Establishment and characterization of new cellular lymphoma model expressing transgenic human MDR1. Leuk Res. 2005 Apr;29(4):407-14. doi: 10.1016/j.leukres.2004.09.001.
14	Mechanisms of thymidine kinase/ganciclovir and cytosine deaminase/ 5-fluorocytosine suicide gene therapy-induced cell death in glioma cells. Oncogene. 2005 Feb 10;24(7):1231-43. doi: 10.1038/sj.onc.1208290.
15	Combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and actinomycin D induces apoptosis even in TRAIL-resistant human pancreatic cancer cells. Clin Cancer Res. 2001 Feb;7(2):407-14.
16	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
17	Johnson EJ, MacGowan AP, Potter MN, et al "Reduced absorption of oral ciprofloxacin after chemotherapy for haematological malignancy." J Antimicrob Chemother 25 (1990): 837-42. [PMID: 2373666]
18	Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
19	Product Information. Prolia (denosumab). Amgen USA, Thousand Oaks, CA.
20	Bennett CL, Nebeker JR, Samore MH, et al "The Research on Adverse Drug Events and Reports (RADAR) project." JAMA 293 (2005): 2131-40. [PMID: 15870417]
21	Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
22	Cerner Multum, Inc. "Australian Product Information.".
23	Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
24	Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
25	Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.
26	Product Information. Arcalyst (rilonacept). Regeneron Pharmaceuticals Inc, Tarrytown, NY.
27	Product Information. Cimzia (certolizumab). UCB Pharma Inc, Smyrna, GA.
28	CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]
29	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.